[unreadable] Lupus in the NZM2410 model is contingent upon at least 3 non-H2 loci- S/e1, S/e2, and S/e3. When introgressed as congenic intervals onto the normal B6 background, these 3 loci lead to very different immunophenotypes. In particular, Sle3 leads to generalized T-cell hyperactivity and a modest degree of anti-nuclear autoreactivity. It is known that the phenotypes associated with S/e3 are bone marrow transferable, but are not T-cell or B-cell intrinsic. Furthermore, it has become clear that S/e3 is also associated with altered numbers and function of dendritic cells and macrophages. The present proposal seeks to understand how S/e3 might be impacting Toll receptor signaling. In particular, biochemical and genetic studies will be carried out to determine if S/e3 might impact the My D88 or TRIF dependent signaling pathways. [unreadable] [unreadable]